22 Hematopoietic Stem Cell Transplantation Chow

Question 1

What are the goals of Pre-Transplant Conditioning (“Negative Days” to Day 0)?

Answer 1

To eradicate as many malignant cells as possible before re-infusion of stem cells. To suppress recipient’s immune system prior to receiving donor stem cells (allHSCT)

Question 2

What are the Immunological Sources of Stem Cells?

Answer 2

Autologous HSCT (recipient’s own stem cells collected previously). Syngeneic HSCT (identical twin’s stem cells). Allogeneic HSCT (donor provides stem cells)

Question 3

What are the different types of Allogeneic HSCT?

Answer 3

Matched related donor (MRD). Mismatched related donor (MMRD). Matched unrelated donor (MUD). Mismatched unrelated donor (MURD)

Question 4

What is Allogeneic HSCT: HLA Matching?

Answer 4

Human Leukocyte Antigen (HLA) encodes the Major Histocompatibility Complex (MHC) genes, which are surface antigens important for compatibility between donor stem cells and host tissues. Matching of HLA-A, -B, and -DR the most critical

Question 5

What is Nonmyeloablative Transplantation (NMT; “mini-allo”)?

Answer 5

Chemotherapy used in conditioning regimen may not completely eliminate tumor cells. Role of conditioning regimen is to immuno-suppress recipients to allow for engraftment of donor stem cells. Rationale: utilizes donor T-cell mediated graft-versus-tumor (GVT) effect that continues to eradicate recipient tumor cells post transplant. This allows the use of stem cell transplantation in elderly patients and/or those who cannot tolerate high dose intensive conditioning regimens

Question 6

Which source of stem cells are less likely to develop chronic GVHD?

Answer 6

Bone Marrow

Question 7

Which source of stem cells is most common but also has a high risk of chronic GVHD?

Answer 7

Peripheral blood

Question 8

What are Peripheral Stem Cell Mobilization agents used for?

Answer 8

To increase the number of CD34+ stem cells that can be collected by leukapheresis of peripheral blood

Question 9

What are the commonly used Peripheral Stem Cell Mobilization agents?

Answer 9

Filgrastim. Sargramostim

Question 10

What is Plerixafor (Mozobil)?

Answer 10

CXCR4 chemokine receptor inhibitor. Mobilizes hematopoietic stem cells to peripheral blood to be collected for autologous transplantation for multiple myeloma and NHL

Question 11

What are the complications with HSCT?

Answer 11

Infection! GVHD! Mucositis! Hematologic toxicities - expected from conditioning regimen. Non-hematologic toxicities: Pulmonary, hepatic, renal, cardiac toxicities, Hepatic veno-occlusive disease, Microangiopathy

Question 12

What are some Post-Transplant Complications?

Answer 12

Toxicities related to conditioning regimen (Nephrotoxicity (cisplatin, ifosfamide), Hepatotoxicity (busulfan, carboplatin), Cardiotoxicity (cyclophosphamide), Mucositis (etoposide, melphalan, TBI)

Question 13

What is Mucositis commonly caused by?

Answer 13

Etp[psode, Melphalan, TBI

Question 14

What are Post-Transplant Infections like?

Answer 14

High risk due to neutropenia, mucositis, immunodeficiency, and central line catheters. Highest risk before engraftment (time of sustained ANC/platelet count without need for transfusion)

Question 15

What is Graft-Versus-Host Disease?

Answer 15

Antigens on host cells activate T-lymphocytes of donor cells, which mount immunologic “attack” on host tissues. Primarily with allogenous HSCT. Staging/grading based on skin, gut, and liver toxicities

Question 16

What is Acute GVHD (< 100 days post transplant)?

Answer 16

Incidence ~25-70%. Risk factors: HLA mismatch, gender mismatch (F:M > F:F > M:M). Older age. Advanced disease stage. High dose of infused stem cells

Question 17

What is used for prevention of acute GVHD?

Answer 17

Start immunosuppression after conditioning chemotherapy is complicated. Choice of immunosuppressant(s) is dependent on the conditioning regimen per institutional protocols

Question 18

What are some common agents used for Prevention of Acute GVHD?

Answer 18

Tacrolimus, Sirolimus, Methotrexate, Cyclosporine

Question 19

What is 1st line treatment for Acute GVHD?

Answer 19

Methylprednisolone! Prednisone, Daclizumab, Infliximab, Beclomethasone

Question 20

What is Chronic GVHD?

Answer 20

> 100 days post transplant. Risk factors: h/o GVHD, HLA mismatch, gender mismatch, older recipient, PBSC

Question 21

What is Limited Chronic GVHD?

Answer 21

Either or both: 1) Localized skin involvement, 2) Hepatic dysfunction d/t chronic GVHD

Question 22

What is Extensive Chronic GVHD?

Answer 22

Either: 1) Generalized skin involvement, or 2) Localized skin involvement and/or hepatic dysfunction d/t chronic GVHD. PLUS. 3a) Liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis, or 3b) Involvement of eye, or 3c) Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy, or 3d) Involvement of any other target organ

Question 23

What is done for treatment of Chronic GVHD?

Answer 23

Treat cGVHD that involves > 3 organs or if > Grade 2 severity in any one organ.

Question 24

What agents are used for treatment of Chronic GVHD?

Answer 24

Prednisone QOD! Prednisone alternating with Cyclosporine QOD. Organ-specific supportive care treatment